The duration of immunity to an inactivated adjuvanted canine parvovirus vaccine. A 52 and 64 week postvaccination challenge study

Dogs were successfully isolated for a period of either 52 or 64 weeks following vaccination with an inactivated, adjuvanted canine parvovirus-2 vaccine. Antibody persisted in all ten vaccinated dogs, although in one case by 52 weeks postvaccination only virus neutralizing antibody, and not hemagglutination-inhibiting antibody, could be detected. Sentinel unvaccinated dogs housed alongside the vaccinated dogs throughout the study remained free of canine parvovirus-2 antibody until challenged. Upon oral challenge with canine parvovirus-2 infected material all unvaccinated dogs developed one or more signs of canine parvovirus-2 disease, shed virus and developed antibody. None of the vaccinated dogs became overtly sick. Of the five vaccinated dogs challenged 52 weeks after vaccination, three shed virus and one showed a significant rise in antibody. At 64 weeks after vaccination only one of the five challenged dogs shed virus and showed a boost in antibody titer.     

The failure of an inactivated mink enteritis virus vaccine in four preparations to provide protection to dogs against challenge with canine parvovirus-2.

Four experimental vaccine preparations comprising a strain of mink enteritis virus inactivated by either formalin or beta-propiolactone, and either adjuvanted or nonadjuvanted, failed to stimulate a consistent serum antibody response in 20 vaccinated dogs and failed to protect all but one of these dogs against oral challenge with canine parvovirus-2.     

Response of mink, skunk, red fox and raccoon to inoculation with mink virus enteritis, feline panleukopenia and canine parvovirus and prevalence of antibody to parvovirus in wild carnivores in Ontario.

Mink virus enteritis, feline panleukopenia and canine parvovirus-2 were inoculated separately into groups of raccoon, mink, red fox and striped skunk. Raccoons were highly susceptible to mink virus enteritis and feline panleukopenia, with animals developing clinical illness, and several dying within six to ten days of inoculation with lesions typical of parvovirus infection. Both viruses were shed in high titre in the feces of infected raccoons, and high antibody titres were stimulated. Raccoons inoculated with canine parvovirus-2 showed no signs; shedding of virus was sporadic though moderate titres of antibody developed. Mink inoculated with mink virus enteritis and feline panleukopenia developed signs and lesions of early parvovirus infection. No signs or significant lesions followed canine parvovirus-2 inoculation. Shedding of virus was heavy (mink virus enteritis) or sporadic (feline panleukopenia and canine parvovirus-2), though good serological responses were elicited to all three viruses. Red fox showed no signs of infection, shed all three viruses only sporadically, and the serological response was strong only to feline panleukopenia. Skunks developed low antibody titres, but no signs, and did not shed virus. Antibody to parvovirus was found in 79.2% of 144 wild red foxes; 22.3% of 112 wild raccoons; 1.3% of 157 wild skunks and 6/7 coyotes in southern Ontario. The likely significance of these viruses to wild and captive individuals and populations of these carnivores is discussed.     

Measles vaccine in dogs: efficacy against aerosol challenge with virulent canine distemper virus.

Fifty young Beagle pups were used in studies on the efficacy of measles virus vaccine in providing protection against virulent canine distemper (CD) virus given intranasally. Among 29 dogs vaccinated with measles virus vaccine and subsequently exposed to virulent CD virus, 1 died, 7 developed relatively severe signs of CD, 15 had mild signs of distemper, and 6 remained clinically normal. Of 15 unvaccinated dogs similarly exposed to virulent CD virus, 11 succumbed to distemper. Six pups vaccinated with modified live-virus (MLV) CD virus vaccine remained clinically normal following immunity challenge.     

Pathogenesis of canine parvovirus-2 in dogs: histopathology and antigen identification in tissues

The pathogenesis of canine parvovirus-2 was studied in orally inoculated conventional dogs using histopathological and peroxidase anti-peroxidase staining techniques. Lymphoid necrosis and depletion of lymphocytes from lymphoid tissues were most notable on days 5 and 6 after exposure. Lymphocyte hyperplasia occurred following day 7. Epithelial cell changes in segments of the small intestine were more severe on days 6 to 9 after exposure in areas associated with Peyer's patches and in the upper segments of the small intestine. The lymphocyte was the primary infected cell. Virus infected cryptal epithelial cells were not detected until 24 hours after the identification of infected cells in lymphoid tissues on day 4 after exposure. The majority of virus infected epithelial cells were found in crypts intimately associated with or adjacent to Peyer's patches in the upper segments of the small intestine.     

The seroprevalence of canine parvovirus-2 in a selected sample of the canine population in ontario

Canine sera, collected from dogs presented to the Ontario Veterinary College between 1976 and 1980, were assessed for canine parvovirus-2 antibody using a microtitre hemagglutination-inhibition test. Special emphasis was made on the period from September 1979 to October 1980 (2892 samples). No antibody was detected in samples collected in 1976 or 1977. The first positive sera were obtained in January 1978. By the end of 1978 antibodies to canine parvovirus-2 were widespread in Ontario dogs and in 1980, 683 of 2191 dogs (31.2%) had antibody. This was before widespread vaccination was being practised and indicates canine parvovirus-2 infection occurred frequently. Evaluation of clinical records of these dogs suggested that most infections had been subclinical.     

Effect of vaccination with recombinant canine distemper virus vaccine immediately before exposure under shelter-like conditions

Vaccination with modified-live virus (MLV) canine distemper virus (CDV) vaccine has historically been recommended for animals in high-risk environments because of the rapid onset of immunity following vaccination. Recombinant CDV (rCDV) vaccine was deemed a suitable alternative to MLV-CDV vaccination in pet dogs, but insufficient data precluded its use where CDV was a serious threat to puppies, such as in shelters, kennels, and pet stores. In this study, dogs experimentally challenged hours after a single dose of rCDV or MLV vaccine became sick but recovered, whereas unvaccinated dogs became sick and died. Dogs vaccinated with a single dose of rCDV or MLV vaccine 1 week before being experimentally challenged remained healthy and showed no clinical signs. Dogs given one dose of rCDV vaccine hours before being placed in a CDV-contaminated environment did not become sick. These findings support the hypothesis that rCDV vaccine has a similar time-to-immunity as MLV-CDV vaccines and can likewise protect dogs in high-risk environments after one dose.     

Three-year duration of immunity in dogs following vaccination against canine adenovirus type-1, canine parvovirus, and canine distemper virus

A challenge-of-immunity study was conducted to demonstrate immunity in dogs 3 years after their second vaccination with a new multivalent, modified-live vaccine containing canine adenovirus type 2 (CAV-2), canine parvovirus (CPV), and canine distemper virus (CDV). Twenty-three seronegative pups were vaccinated at 7 and 11 weeks of age. Eighteen seronegative pups, randomized into groups of six dogs, served as challenge controls. Dogs were kept in strict isolation for 3 years following the vaccination and then challenged sequentially with virulent canine adenovirus type 1 (CAV-1), CPV, and CDV. For each viral challenge, a separate group of six control dogs was also challenged. Clinical signs of CAV-1, CPV, and CDV infections were prevented in 100% of vaccinated dogs, demonstrating that the multivalent, modified-live test vaccine provided protection against virulent CAV-1, CPV, and CDV challenge in dogs 7 weeks of age or older for a minimum of 3 years following second vaccination.     

Pathogenesis of canine parvovirus-2 in dogs: haematology, serology and virus recovery

The pathogenesis of canine parvovirus-2 (CPV-2) was studied in orally inoculated conventional dogs using haematological, serological and virological techniques. Virus was first isolated from mesenteric lymph nodes on day 2 after exposure, tonsil on day 3 and small intestine on day 3. Viraemia occurred subsequently and was present in most dogs on days 4 and 5 after exposure. CPV-2 could be isolated from all tissues during viraemia. Relative pyrexia, lymphopenia and neutropenia occurred on days 5, 6 and 7 after exposure, respectively. Virus excretion in faeces began in most dogs on day 4 and continued despite the appearance of neutralising serum antibody. Specific serum antibody, detected in some dogs as early as day 3 and in all dogs by day 7 after exposure, eliminated viraemia and inhibited virus isolation from tissues in cell culture.     

Vaccination of Tunisian dogs with the lyophilised SAG2 oral rabies vaccine incorporated into the DBL2 dog bait

The protective effect of the lyophilised SAG2 oral vaccine bait DBL2, already demonstrated on laboratory dogs, needed to be verified on common Tunisian dogs. Seven Tunisian dogs consumed totally or partially one DBL2 bait containing 10(8.3) TCID50 of the highly attenuated rabies vaccine strain, SAG2. Five of the seven vaccinated animals survived a challenge administered 33 days later with a Tunisian canine street rabies virus to which five of the six controls that were not vaccinated and had no specific antibodies succumbed. The partial or total consumption of a single DBL2 bait thus conferred a protective immune response similar to that observed in laboratory dogs to dogs of poor health status. The sero-antibody response was, however, weak: only two vaccinated dogs exhibited a significant neutralising antibody response after vaccination and before the challenge, and four after the challenge.     

Characterization of minute virus of canines (MVC) and its pathogenicity for pups

Minute virus of canines (MVC, canine parvovirus-1), originally isolated in 1970 from the feces of normal dogs, was compared with canine parvovirus type-2 (CPV-2). The two viruses, which differ in their host cell ranges and spectra of hemagglutination, also were found distinct in their antigenic and genomic properties. We demonstrated that the MVC replicates in dogs and is capable of producing pathologic changes that were most prominent in oronasally-exposed neonatal pups. Macroscopic and microscopic lesions were most prominent in the thymus and lymph nodes; minor changes were found in the duodenal crypts. The MVC strain used had been passaged 13 times in cell cultures and it may not represent the true virulence of naturally occurring virus.     

Treatment of canine parvoviral enteritis with interferon-omega in a placebo-controlled challenge trial

Canine parvoviral enteritis continues to cause significant morbidity and mortality in dogs worldwide, and efficacious antiviral therapies are lacking. The present trial was aimed at evaluating the therapeutic efficacy of a recombinant feline interferon (type omega) preparation in the treatment of parvoviral enteritis in dogs. A double-blind, placebo-controlled challenge trial was performed in beagle pups (8-9 weeks); clinical signs, body weight, hematologic parameters, and mortality were monitored for a period of 14 days after challenge. Fourteen animals were inoculated with virulent canine parvovirus; 10 animals that developed clinical signs thereby meeting the inclusion criteria were admitted to the treatment phase in two randomly selected groups (placebo and IFN) of equal size. The IFN group received daily intravenous injections of rFeIFN-omega (2.5 MU/kg) for three consecutive days. The placebo group received daily injections of saline without IFN. Both groups of animals received individual supportive treatment consisting of adjusted diet and electrolyte solution.All five dogs in the placebo group developed fulminating enteritis with typical clinical signs and died within 10 days post-inoculation (or 6 days post-treatment). In the IFN-treated group, one animal died on day 2 after the treatment was started, whereas the other four dogs survived the challenge and gradually recovered. Our data confirm that the rFeIFN-omega can exert a significant therapeutic effect on dogs with parvoviral enteritis by improving clinical signs and reducing mortality.     

Three-year rabies duration of immunity in dogs following vaccination with a core combination vaccine against canine distemper virus, canine adenovirus type-1, canine parvovirus, and rabies virus

Thirty-two seronegative pups were vaccinated at 8 weeks of age with modified-live canine distemper virus (CDV), canine adenovirus type-2 (CAV-2), and canine parvovirus (CPV) vaccine and at 12 weeks with a modified-live CDV, CAV-2, CPV, and killed rabies virus vaccine. An additional 31 seronegative pups served as age-matched, nonvaccinated controls. All test dogs were strictly isolated for 3 years after receiving the second vaccination and then were challenged with virulent rabies virus. Clinical signs of rabies were prevented in 28 (88%) of the 32 vaccinated dogs. In contrast, 97% (30 of 31) of the control dogs died of rabies infection. These study results indicated that no immunogenic interference occurred between the modified-live vaccine components and the killed rabies virus component. Furthermore, these results indicated that the rabies component in the test vaccine provided protection against virulent rabies challenge in dogs 12 weeks of age or older for a minimum of 3 years following vaccination.     

High-cell-passage canine coronavirus vaccine providing sterilising immunity

OBJECTIVES: To evaluate the ability of a high-cell-passage canine coronavirus vaccine to immunise dogs against challenge with a field isolate of the virus. METHODS: Three dogs that had previously tested seronegative and virus-negative for canine coronavirus were inoculated twice, at 21-day intervals, with the vaccine and kept under observation. Two seronegative and virus-negative dogs served as unvaccinated controls. For safety tests, two additional dogs were inoculated oronasally with 10 times the vaccinal dose and no reactions were observed. Faecal samples were collected daily from the vaccinated dogs after the first and second inoculations. Both vaccinated and control dogs were challenged two weeks after the second vaccination with a field canine coronavirus strain. Blood samples were collected for serological tests before vaccination and at weekly intervals after vaccinations and challenge. RESULTS: Virus was not detected in faecal samples after the first or second vaccinations by virus isolation assays and PCR. Significantly, the vaccinated dogs did not have clinical signs after challenge and no virus shedding was observed. The two unvaccinated control dogs had moderate enteritis, and virus was detected in cell cultures starting from three days postchallenge (dog 1) and two days postchallenge (dog 2), and by PCR for 23 median days. CLINICAL SIGNIFICANCE: This study showed the efficacy of a high-cell-passage canine coronavirus vaccine in preventing infection of dogs by virulent virus and, specifically, its ability to induce sterilising immunity.     

Pathogenesis of canine parvovirus enteritis: sequential virus distribution and passive immunization studies

After oral inoculation, the sequential distribution of canine parvovirus was studied in 14 nine-week-old seronegative beagle dogs. Two or three dogs were necropsied on days 1 through 6 after inoculation. Tissues were collected for virus isolation, immunofluorescence testing, and light microscopy. Virus was isolated from, and fluorescent cells were seen in the tonsil, retropharyngeal and mesenteric lymph nodes one and two days after inoculation. Virus infection of systemic and intestinal lymphoid tissues occurred as early as three days after inoculation and was associated with viremia. Intestinal epithelial infection was first seen four days after oral inoculation. All dogs were viremic before intestinal epithelial infection was found. Fecal virus excretion first occurred four days after oral virus inoculation. Intestinal virus infection and lesions became progressively more severe between four and six days after inoculation. The severity of intestinal lesions was variable and related to the severity of systemic lymphoid tissue lesions and the magnitude and duration of viremia. Four littermates of virus-infected dogs were passively immunized against canine parvovirus with convalescent canine serum 24 hours after oral virus inoculation. Neither clinical signs, lymphopenia, nor fecal virus excretion occurred in passively immunized dogs. Intestinal epithelial infection was not demonstrable by immunofluorescence testing when passively immunized dogs were necropsied four, five, and six days after virus inoculation.     

Prevention of renal infection and urinary shedding in dogs by a Leptospira vaccination

Prevention of urinary shedding of Leptospira interrogans spp. by chronically infected dogs remains a key objective of the vaccination in dogs against leptospirosis which is a zoonotic disease. An inactivated bivalent vaccine composed of Leptospira interrogans serovars icterohaemorrhagiae [L. icterohaemorrhagiae] and canicola [L. canicola] bacterins was tested for its ability to protect puppies against a challenge exposure with L. icterohaemorrhagiae. The vaccine was administered twice at a 3-week interval to six puppies aged from 8 to 9 weeks. Six other puppies were used as unvaccinated controls. All puppies were challenged 2 weeks after the second vaccine injection by intraperitoneal (IP) administration of L. icterohaemorrhagiae (day 0). Clinical signs, haematological and biochemical changes and evidence of Leptospira in blood, urine and kidney were monitored for 4 weeks after the challenge exposure (days 0-28). Puppies were euthanised on day 28 for post-mortem and histological examinations of liver and kidney. Control group presented clinical pictures of severe or subclinical infection. One dog developed severe clinical signs (hypothermia, depression, anorexia, abdominal pain, dehydration, icterus, weight loss) and died on post-infection day (PID) 7 due to an acute renal failure. Gross and microscopic lesions were in accordance with this clinical pattern. In the five remaining control dogs, the challenge exposure induced mainly a systemic infection including leptospiraemia, leptospiruria and renal carriage. The vaccinated group remained healthy throughout the study period. In conclusion, immunisation with a Leptospira vaccine was shown to protect dogs against symptomatology and leptospiraemia, urine shedding and renal infection.     

Assessment of toxicosis induced by high-dose administration of milbemycin oxime in collies

Fifteen Collies, previously having mild reactions to ivermectin challenge (120 micrograms/kg of body weight; 20 times the recommended dosage level), were studied to evaluate the effects of milbemycin oxime administration at 5 and 10 mg/kg (10 and 20 times the manufacturer's recommended dosage). Five replicates, comprising 3 dogs each, were formed on the basis of body weight. Within replicates, each dog was randomly allocated to treatment with 5 or 10 mg of milbemycin/kg or served as a untreated control. Dogs were examined repeatedly for signs of toxicosis for 4 days after treatment and daily thereafter. Two of 5 dogs treated at 5 mg/kg (10x) developed signs of mild depression on the day of treatment, but were normal 24 hours after treatment. All 5 dogs treated at 10 mg/kg (20x) developed signs of mild depression and ataxia by 6 hours. Signs persisted for 24 hours in 3 dogs. Two of these dogs also had mydriasis, whereas 3 salivated excessively. All dogs recovered completely by day 2 after treatment. The results of this study demonstrated that Collies sensitive to the effects of 120 micrograms of ivermectin (20x)/kg show similar sensitivity to the effects of milbemycin oxine administered at 10 mg/kg (20x). We conclude that ivermectin and milbemycin commercial formulations have similar margins of safety and that milbemycin toxicosis appears to be dose-dependent in Collies with a demonstrated sensitivity to ivermectin.     

Postexposure prophylaxis for prevention of rabies in dogs

OBJECTIVE: To evaluate postexposure prophylaxis (PEP) in dogs experimentally infected with rabies. ANIMALS: 29 Beagles. PROCEDURE: Dogs were sedated and inoculated in the right masseter muscle with a salivary gland homogenate from a naturally infected rabid dog (day 0). Six hours later, 5 dogs were treated by administration of 2 murine anti-rabies glycoprotein monoclonal antibodies (mAb) and commercial vaccine; 5 received mAb alone; 5 received purified, heat-treated, equine rabies immune globulin (PHT-ERIG) and vaccine; 5 received PHT-ERIG alone; 4 received vaccine alone; and 5 control dogs were not treated. The mAb or PHT-ERIG was administered at the site of rabies virus inoculation. Additional vaccine doses for groups mAb plus vaccine, PHT-ERIG plus vaccine, and vaccine alone were administered IM in the right hind limb on days 3, 7, 14, and 35. RESULTS: All control dogs and dogs that received only vaccine developed rabies. In the PHT-ERIG and vaccine group, 2 of 5 dogs were protected, whereas none were protected with PHT-ERIG alone. Use of mAb alone resulted in protection in 4 of 5 dogs. Administration of mAb in combination with vaccine provided protection in all 5 dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Current national guidelines recommend euthanasia or a 6-month quarantine for unvaccinated animals exposed to rabies. Findings from this study document that vaccine alone following severe exposure was unable to provide protection from rabies. However, vaccine combined with mAb resulted in protection in all treated dogs, revealing the potential use of mAb in PEP against rabies in naive dogs.     

Effects of milbemycin on adult Toxocara canis in dogs with experimentally induced infection

To determine the efficacy of a formulation of milbemycins in treating patent infection with Toxocara canis, 8 male and 7 female, 10-week-old, ascarid-free Beagles each were given 125 embryonated eggs of T canis. All dogs developed patent infection within 56 days. On post-infection day 70, the dogs were assigned to 1 of 3 groups of 5 dogs each; members of 1 group were given a placebo, while dogs of the other 2 groups were given either 5.68 or 34.08 mg of the milbemycin formulation, respectively. In both groups of dogs given the drug, the number of eggs passed per gram of feces decreased precipitously. However, a few eggs still were found in the feces of several dogs of each group on the day of necropsy (postinfection day 75). Worms or fragments of worms were passed by the treated dogs from the day of treatment until the day on which necropsy was performed; however, most worms were passed during the first 2 days after treatment. At necropsy, only dogs of the control group were found to harbor adult T canis.     

Vaccination with canine parvovirus type 2 (CPV-2) protects against challenge with virulent CPV-2b and CPV-2c

Mutations in canine parvovirus (CPV) field isolates have created concerns regarding the ability of vaccines containing CPV-2 to protect against infection with the newly identified antigenic types CPV-2b and CPV-2c. To address this concern, the efficacy of CPV-2 strain NL-35-D currently in use as a commercial vaccine was demonstrated against an oral challenge with CPV-2b and CPV-2c, respectively. Clinically healthy specific pathogen free Beagle dogs were either vaccinated or treated with water for injection first at 8-9 weeks of age and again at 11-12 weeks of age. All dogs were challenged either with CPV-2b or CPV-2c three weeks after the second vaccination. During the two week period following challenge, clinical signs, white blood cell counts, serology by haemagglutination inhibition (HI) and serum neutralisation tests, and virus shedding by haemagglutination test were assessed. All control dogs developed clinical signs of parvovirosis (including pyrexia and leucopenia) and shed virus. Vaccinated dogs seroconverted (HI titres > or =80), remained healthy throughout the study and shed more than 100 times less virus than controls. In conclusion, vaccination with the low passage, high titre CPV-2 strain NL-35-D cross-protects dogs against virulent challenges with CPV-2b or CPV-2c by preventing disease and substantially reducing viral shedding.